The objective of this research proposal is to purify the IP3 (inositol 1.4.5-triphosphate) receptor from human platelets and pituitary tumor GH3 cells. This receptor is a protein that binds IP3 and thereby mediates the release of intracellular stores of Ca 2+ in a wide variety of cells: e.g. endocrine glands, liver, platelets, smooth muscle, cells of the immune and central nervous systems, photoreceptor cells, eggs, etc. IP3 is a mediator of the action of many hormones, peptides, transmitters, immunomediators and other agonists. Therefore, understanding its mechanism of action and the isolation of the IP3 receptor and the CA 2+ channel system is of great importance to many fields of biology. The research described in this proposal is directed towards identification and purification of the IP3 receptor, determination of its intracellular localization, and investigation of its molecular properties. Two cell types will be used for these studies, the human platelet and the pituitary tumor cell line GH3.